The polycystic ovarian syndrome was originally described in 1935 by Stein and Leventhal as a syndrome manifested by

1. POLYCYSTIC OVARIAN
SYNDROME (PCOS)
Prepared by
Dr. Abdulkarim Jabra
OBGYN dep. at second
Hospital of Jilin university
1

2. OUTLINES
 Introduction of PCOS
 Etiology
 Incidence
 Diagnosis
 Pathophysiology
 Clinical features
 Investigations
 Complication of PCOS
 Management
 PCOS and COVID-19
 Pregnancy complications

3. Scenario
 A 32 years old female complains of vaginal
bleeding. Facial hair growth present for many
years, but the irregular bleeding has been getting
worse during the past 6 months. On pelvic
examination she has slightly enlargeness
bilateral ovaries.

4. Introduction
Polycystic ovarian syndrome was originally
described in 1935 by Stein and Leventhal
as a syndrome manifested by
 Amenorrhea,
 Hirsutism, and
 Obesity associated with enlarged polycystic ovaries.
It is the most common endocrine disorder in a
woman of reproductive age affecting
approximately 6 to 16% in general population.

5. Other names for this syndrome include
 Polycystic ovary disease
 Functional ovarian hyperandrogenism
 Ovarian hyperthecosis
 Sclerocystic ovary syndrome, and
 Stein–Leventhal syndrome.

6. Etiology
This heterogeneous disorder is
characterized by excessive androgen
production by the ovaries mainly.
 PCOS is a multifactorial and polygenic condition.
 The underlying cause of PCOS is Unknown.
 A combination of genetic and environmental factors were added as
aetiological factors in the development of PCOS.
PCOS is thought to have a dominant mode
of inheritance as about 50% of first degree
relatives have PCOS.

7. Etiology
continued…
Risk factors include obesity, a lack of physical
exercise, and a family history of someone with the
condition. High maternal androgens, insulin
resistance, onset of type1 DM before menarche
and drugs.
PCOS has been attributed to several causes
including change in lifestyle, diet and stress.

8. PCOS occasionally seen in pre-pubertal age
Risk factors for prepubertal adolescents are
1. Low birth weight
2. Premature adrenarche
3. Atypical sexual activity
4. Obesity with acanthosis nigricans
Diagnosis of PCOS in adolescent age group is
difficult, because many symptoms of PCOS mimic
the normal physiologic responses of puberty.

9. Polycystic ovarian syndrome may set in
early adolescent life, but clinically manifest
in the reproductive age with long-term
implications of diabetes, hypertension,
hyperlipidaemia and cardiovascular disease;
this cluster of disorders is known as the
metabolic ‘X syndrome’.

10. Polycystic ovary syndrome: a complex condition with psychological,
reproductive and metabolic manifestations that impacts on health across
the lifespan

11. Incidence
The incidence varies between 0.5–4 percent, more
common amongst infertile women.
 It is prevalent in young reproductive age group
(20–30%).
Polycystic ovary may be seen in about 20% of
normal women.
Most patients with PCOS are obese (BMI
≥30kg/m2), but can occur in thin female.
Amongst infertile women, about 20% infertility is
attributed to anovulation caused by PCOS.

12. Diagnosis
Is based upon the presence of any two of
the following three criteria [American society for
reproductive medicine (ASRM)/ European society of human
reproduction and embryology (ESHRE), 2003]
 Oligo and/or anovulation.
 Hyperandrogenism (clinical and/or biochemical).
 Polycystic ovaries.
These signs and symptoms vary widely
between women and within individuals over
time.

13. When evaluating for PCOS, it is important to rule out
other endocrinopathies.
Differential diagnoses for patients who have
PCOS can include
 Endocrine androgen-secreting tumors, pseudo-PCOS
related to obesity, insulin resistance, sex development
disorders
 Congenital adrenal hyperplasia (CAH)
 Thyroid dysfunction
 Hyperprolactinemia
 Cushing syndrome and
 Androgenic drugs

14. Dx criteria of PCOS..ctd

15. Diagnostic criteria
continues….
1. AE-PCOS =Androgen
Excess and PCOS
Society;
2. ASRM = American
Society of Reproductive
Medicine;
3. ESHRE = European
Society of Human
Reproduction and
Embryology;
4. NIH = National Institutes
of Health.
5. PCOS = polycystic
ovarian syndrome

16. History and physical examination
 There is need for careful clinical assessment of
women's history, physical examination, and laboratory
evaluation, emphasizing the accuracy and validity of the
methodology used for both biochemical measurements and
ovarian imaging.
 History of lifestyle, diet and smoking and exogenous
hormone administration should be inquired into.
 Family history of diabetes and hypertension should be
asked.
 Excessive exercise, history of tuberculosis and thyroid are
important in menstrual disorder.

17. Pathology
Typically, the ovaries are enlarged.
 Ovarian volume is increased > 10 cm3.
Stroma is increased.
The capsule is thickened and pearly white in
colour.
Presence of multiple (> 12) follicular cysts
measuring about 2–9 mm in diameter are
crowded around the cortex (Fig. 29.4).

19. Histology
There is thickening of tunica albuginea.
The cysts are the follicles at varying stages
of maturation and atresia.
There is theca cell hypertrophy (stromal
hyperthecosis).
Patient may present with features of
diabetes mellitus (insulin resistance).

20. Pathophysiology
 Exact pathophysiology of PCOS is not clearly understood. It may
be discussed under the following heads (scheme–1):
1. Hypothalamic-pituitary compartment
abnormality
2. Androgen excess and hirsutism
3. Anovulation
4. Obesity and insulin resistance
5. Long-term consequences.

23. 1. Hypothalamic-pituitary Compartment in PCOS
• Increased pulse frequency of GnRH leads to
increased pulse frequency of LH.
• Leptin (a peptide, secreted by fat cells and
by the ovarian follicle), insulin resistance and
hyperandrogenemia are responsible for this.
• GnRH is preferential to LH rather than FSH
• The LH : FSH ratio is increased.

24. 2. Androgen Excess
Abnormal regulation of the androgen
forming enzyme (P450 C17) is thought to be
the main cause for excess production of
androgens from the ovaries and adrenals.
The principal sources of androgens are
 Ovary (scheme–3).
 Adrenal
 Systemic metabolic alteration (Hyperinsulinemia and
Hyperprolactinemia)

25. Pathophysiology schemes

26. Major androgens in female
In female major androgens are:
 Dehydroepiandrosterone sulfate (DHEA-S)
 Dehydroepiandrosterone (DHEA)
 Androstenedione
 Testosterone (T) and
 Dihydrotestosterone (DHT).
 All androgenic activities are due to T and DHT.

27. The sources of androgens in normal female are
schematically depicted in Flow chart.

28. 3. Anovulation
• Because of low FSH level, follicular growth
is arrested at different phases of maturation
(2–10 mm diameter).
• The net effect is diminished estradiol and
increased inhibin production.
• Due to elevated LH, there is hypertrophy of
theca cells and more androgens are
produced either from theca cells or stroma
(scheme–5).

29. • There is defective FSH induced
aromatization of androgens to estrogens.
• Follicular microenvironment is therefore
more androgenic rather than estrogenic.

30. This picture from Kaplan medical

31. 4. Obesity and Insulin Resistance
• Obesity (central) is recognized as an
important contributory factor.
• Apart from excess production of androgens,
obesity is also associated with reduced
SHBG.
• It also induces insulin resistance and
hyperinsulinemia which in turn increases the
gonadal androgen production.

32. 5. Long-term consequences in patient
Long-term consequences in a patient suffering from
PCOS includes:
• The excess androgens (mainly androstenedione) either
from the ovaries (mainly) or adrenals are peripherally
aromatized to estrone (E1).
• There is concomitant diminished SHBG.
• Cumulative excess unbound E2 and estrone results in
a tonic hyperestrogenic state (scheme–6).
• There is endometrial hyperplasia.

33. Scheme 6

35. Clinical Features
The patient complains of:
 increasing obesity (abdominal—50%)
 menstrual abnormalities (70%) in the form of:
 Oligomenorrhea,
 Amenorrhea or dysfunctional uterine bleeding (DUB) and
 Infertility.
 Presence of hirsutism and acne are the
important features (70%). Virilism is rare.

36. Symptoms and signs of PCOS
The symptoms of
polycystic ovary
syndrome (PCOS) include
•menstrual cycle
disturbance and
features of
hyperandrogenism
(hirsutism, acne and
alopecia), with
associated fertility
problems, obesity and
psychological issues.

37. Clinical features of PCOS
continues….

38. Acanthosis nigricans
Acanthosis nigricans is characterized by
specific skin changes due to insulin
resistance.
The skin is thickened and pigmented (gray
brown).
Commonly affected sites are nape of the
neck, inner thighs, groin and axilla

39. HAIR-AN syndrome
HAIR-AN syndrome in patients with PCOS
is characterized by
• Hyperandrogenism (HA)
• Insulin resistance (IR) and
• Acanthosis nigricans (AN).
Internal examination reveals bilateral
enlarged cystic ovaries which may not be
revealed due to obesity.

41. Male Pattern Escutcheon.

42. Ovarian hyperthecosis
Ovarian hyperthecosis, often considered a more
severe form of PCOS, is a rare condition
characterized by nests of luteinized theca cells
distributed throughout the ovarian stroma.
Affected women exhibit severe hyperandrogenism
and greater degree of insulin resistance.

43. Investigations
1. Sonography:
• Transvaginal sonography (TVS) is specially
useful in obese patient.
• Ovaries are enlarged in volume (≥10 cm3).
• Increased number (> 12) of peripherally
arranged cysts (2–9 mm) are seen (Fig.
29.7).

45. 2. Serum values:
 LH level is elevated and/or the ratio LH: FSH is
> 2:1.
 Raised level of estradiol and estrone ─ (the
estrone level is markedly elevated).
 SHBG level is reduced.
 Raised serum testosterone (> 150 ng/dL) and
dehydro-epiandrosterone sulfate (DHEAS) may
be marginally elevated.

46. 3. Insulin resistance (IR):
 Raised fasting insulin levels > 25 μIU/mL
and fasting glucose/insulin ratio < 4.5
suggests IR (50%).
 Levels of serum insulin response > 300
μIU/mL at 2 hours post-glucose (75 gm)
load, suggests severe IR.

48. 4. Laparoscopy:
 Bilateral polycystic ovaries are characteristic
of PCOS.

49. Investigations in a Case of PCOS
• Ultrasonography (transvaginal preferred).
• Reassessment of: BMI, BP (blood pressure),
waist circumference.
• Serum levels of: FSH, LH, TSH, total
testosterone, prolactin, DHEAS, 17 OHP, cortisol.
• 2 hour oral glucose tolerance test (GTT),
HbA1c
• Lipid profile: LDL,HDL, TG

50. Metabolic syndrome Dx Criteria

51. Complications of PCOS

52. Management: Polycystic Ovarian
Syndrome (PCOS)
Management of PCOS needs individualization
of the patient.
• It depends on her presenting symptoms, like
• Menstrual disorder
• Infertility,
• Obesity,
• Hirsutism or combined symptoms.
• Patient counseling is important.

53. The purpose of treatment is:
2. Conduct appropriate diagnostic workup
3. To resolute anovulation and infertility
4. To prevent of endometrial hyperplasia and
cancer.
1. To restore normal menstruation
2. To improve lifestyle, hyper-androgenic state
(hirsutism and acne) and insulin sensitivity

54.  Treatment is primarily targeted to correct
the biochemical abnormalities (Table
29.5).

56. Conservative Treatment
Women with PCOS who have fairly regular cycle
intervals (8 to 12 menses/year) and mild
hyperandrogenism may choose not to be
treated. however, periodic screening for
dyslipidaemia, DM, and metabolic syndrome is
reasonable.
For obese women with PCOS, important lifestyle
changes focus on diet and exercise.
 Weight reduction in obese patients is the first line of
treatment. Exercise is found beneficial. Diet is one
important element.

57. IMPROVE lifestyle in polycystic ovary syndrome
 Lifestyle change is the first-line of treatment for
the management of women with PCOS, however
obtaining long-term adherence is challenging.
 In order to improve adherence to advice on
lifestyle, we propose a strategic systematic
approach that could be easily remembered with
the acronym I.M.P.R.O.V.E.: Inform, Motivate,
Prescribe, Reward, Oversee, Visualize, Empower.

58. I.M.P.R.O.V.E
Inform Inform the patient that PCOS could be improved with a healthier
lifestyle
Motivate Assess the main underlying concerns for each woman to optimize
adherence through motivation
Prescribe Advice on lifestyle as precisely as if it were a drug, tailored
specifically to the individual and appropriately dosed
Reward Reward restrictions prescribed in conjunction with satisfactory
activities based on patient preference
Oversee Oversee adherence to advice on lifestyle during follow-up
conlsutations
Visualize Visualize measurable changes to reinforce adherence
Empower Empower patients to reinforce and keep lifetime adherence

59. Improving lifestyle

60. Fertility not Desired
Management of hyperandrogenemia.
1. Combined oral contraceptive pills are
effective.
 A first line treatment for menstrual irregularities is combination oral contraceptive
pills (COCs), which induce regular menstrual cycles, lower androgen levels, and thin
the endometrium). Dianette (which contains ethinyloestradiol (35μg) in
combination with cyproterone acetate (2 mg).
• In patients who are not candidates for
combination hormonal contraception, progesterone
withdrawal is recommended every 1 to 3 months.

62.  Hirsutism is due to anovulation, high androgen and insulin
levels, decreased hepatic SHBG production. Correction of
metabolic syndrome improves it.
 Hirsutism: Antiandrogens (cyproterone acetate, spironolactone,
flutamide) may be used.
• The drugs take 3–6 months before the effect on hirsutism is noted.
 Acne treatment is similar to that for hirsutism and involves lowering of
androgen levels.
 Mild acne may be treated with benzoyl peroxide or topical
retinoid monotherapy.
 Moderate to severe acne may require triple therapy (combined with
oral retinoids or oral antibiotics).

63. Other antiandrogens
Dexamethasone: It acts by suppressing pituitary-
adrenal axis. It is used in adrenal or mixed adrenal
and ovarian hyperandrogenism. The dose varies
from 0.25–1 mg daily at bed time.
Spironolactone: It is an aldosterone antagonist
and acts as a potassium sparing diuretic. It inhibits
5α -reductase activity directly. 100–200 mg is
given daily and the maintenance dose is 25–50
mg daily.

64. Flutamide: It is a
nonsteroidal antiandrogen.
It blocks the androgen
receptors as well as it
inhibits testosterone
biosynthesis. It is given in a
dose of 100–200 mg daily
Finasteride: It inhibits
5α-reductase activity.
It improves hirsutism
significantly without
any side effects. Daily
dose is 5 mg.
 Ketoconazole: inhibits the enzyme for androgen
synthesis. A dose of 200mg daily is adequate to
reduce the level of androgens.

65. 2. Metabolic syndrome
in PCOS patients, the incidence of insulin
resistance is 50-80%. Insulin resistance is
associated with diabetes mellitus, central obesity,
dyslipidemia and hypertension.
Metformin, increases insulin sensitivity,
decreases weight and BMI and reduces low-
density lipoprotein (LDL) cholesterol, blood
pressure and the risk of developing diabetes.

66. Metformin improves metabolic syndrome by
reducing all the parameters:
 Weight, BMI (hyperinsulinemia, hyperandrogenism), BP and
lipid abnormalities.
 Metformin 500mg thrice daily is found to correct the
biochemical abnormalities.
 Metformin is used as an oral insulin sensitizing agent.
Pioglitazone and rosiglitazone are also being used
in cases, resistant to metformin.

67. Adverse effects
 Adverse effects of antiestrogens include
Hot flushes
Ovarian hyperstimulation syndrome (OHSS)
 Abdominal discomfort and
 Multiple pregnancies.
Adverse effects of metformin, such as nausea, vo
miting and other gastrointestinal disturbances.

68. Endometrial hyperplasia
• Endometrial hyperplasia causes abnormal
uterine bleeding. Endometrial biopsy may
have to be done (persistent bleeding).
• Chronic anovulation, hyperestrogenemia,
obesity, and hyperinsulinemia cause endometrial
hyperplasia even endometrial cancer.
• Combined oral contraceptives (COCs) is the
treatment of choice to prevent endometrial
hyperplasia and abnormal bleeding.

69. Psychologic Health
Women with PCOS may present with various
psychosocial problems such as anxiety,
depression, eating disorders, and negative
body image. though under-recognized, seem to
affect 28%–64% of women with PCOS, and less
than 5% of these women are satisfied with the
counseling they receive.
For those diagnosed with PCOS, screening for
depression and anxiety is recommended.

70. Patient Desires Pregnancy
Infertility
Infertility or subfertility is a frequent complaint in
women with PCOS and results from anovulatory
cycles. Moreover, in women with infertility
secondary to anovulation, PCOS is a common
cause.
The most common cause of anovulation is
polycystic ovary syndrome(PCOS), which affects
70% of women with anovulation.

71. Evaluation for Patients Presenting With Infertility

73. • Chronic anovulation is the common cause of
infertility. Improvement of metabolic syndrome is
essential.
1. Ovulation induction is usually achieved by
clomiphene citrate (CC) or Letrozole
following correction of other biochemical
abnormalities.
2. In unresponsive cases, pure FSH or
(HMG) along with (hCG) may be managed.

74. Improving metabolic syndrome is essential
continue…
3. Insulin sensitizers: Women with PCOS and
hyperinsulinemia with BMI > 25, ovulate satisfactorily
when clomiphene is combined with metformin.
4. Surgery: Laparoscopic ovarian drilling (LOD) is
done for cases found resistant to medical therapy.
Ovulation occurs in 80–90% and pregnancy in 60–
70%. Not associated risk of multiple pregnancies.
5. Bariatric surgery may be indicated in some
PCOS women who are morbidly obese. Esp. women
with (BMI >35kg/m2) are considered.

75. Metformin is improving clinical pregnancy and ov
ulation rates, but failed to improve livebirth rates w
hen used alone or in conjunction with clomiphene i
n patients with PCOS.
Women who ovulate with clomiphene but who do
not conceive may be offered clomiphene
stimulated intrauterine insemination, before
proceeding to IVF if necessary.

76. LOD Bariatric surgery

77. ART Treatments for Infertility
IVF with embryo transfer (IVF-ET)
Gamete intrafallopian transfer (GIFT)
Zygote intrafallopian transfer (ZIFT)
Cryopreservation
Intracytoplasmic sperm injection (ICSI)

78. Pregnancy complication in PCOS
 Women with PCOS who
become pregnant
experience an increases
rate (30-50%) of early
miscarriage.
 Pregnancy induced
hypertension (PIH)
Others complication:
 Gestational
diabetes (GD)
 Prenatal mortality
 Preterm Birth
 Increased pregnancy
loss in the form of
abortion

79. Lately, some gynecologists used
 To improve the pregnancy rate in PCOS, instead
of metformin, some gynecologists have started
using N-acetyl cysteine with micronutrients.
This reduces the homocysteine level.
The micronutrients include vitamin D, minerals,
chromium, selenium, inositol and folic acid
(ovacare, one tablet twice daily).
Recommended dosage/application : 1-2 Tablets
daily or as directed by the physician.

80. Combination therapy (Trazer F ForteTM)
 Combined therapy of
 insulin sensitizing agents (myo-inositol, D-chiro-
inositol and chromium picolinate),
 antioxidants (N-acetylcysteine and lycopene), and
 vitamins (vitamin D, biotin and folic acid)
 Trazer F Forte tablet is safe and effective in
obese and non-obese women with PCOS.

81. Efficacy of combination therapy of
inositols, antioxidants and vitamins

83. Herbal medicine (Femitex-SP4) in
managing PCOs.

85. Coronavirus Disease 2019 (SARS-CoV-2) and polycystic
ovarian disease: is there a higher risk for these women?

86. Ctd…

87. Summary
 Polycystic ovary is a multisystem endocrinopathy with
features of oligomenorrhoea, non-ovulation, obesity and
hirsutism. It is a disease of young women.
 PCOS originates from insulin resistance; hyperinsulinaemia
and obesity are linked.
 PCOS causes oligomenorrhoea, hirsutism and infertility.
 Ultrasound is the gold standard investigation in the
diagnosis of PCOS. Hormonal study is performed only if
required.

88.  Decrease in weight and change of life style improves the condition
considerably.
 Hormone therapy is catered to the individual requirement.
 Surgery is performed if medical therapy fails and to improve fertility
rate.
 Complete cure should be ensured to avoid late sequel such as
diabetes, hypertension, cardiovascular disease and hyperlipidaemia.
 Raised E2 level, LH level and androgens with low or normal FSH
characterize this syndrome.
 Clomiphene remains the first line of treatment for infertility in PCOS.
Resistant cases require laparoscopic puncture or gonadotropins and
metformin

89. Reference
> DC Dutta's textbook of gynaecology
> Williams textbook of Gynecology
> Howkins & Bourne Shaw’s Textbook of
Gynaecology
> Sakshi Arora of Gynecology
> https://pubmed.ncbi.nlm.nih.gov/33065278/

90. Thanks for your attention, Goodbye
everyone